Recent outbreaks of highly pathogenic H5N1 avian flu virus infection in poultry and humans have raised concerns that a new influenza pandemic may occur in the near future(1). Considering the high mortality associated with H5N1 avian flu, which has ranged from 45% to 81%(2,3), and the limited efficacy of current vaccines and drugs(4,5), development of novel strategies for prevention and treatment of avian flu H5N1 viral infection is urgently needed.
H5N1 avian flu virus belongs to influenza A virus, which is an enveloped, negative-stranded RNA virus. The unique property of being a single-stranded RNA virus makes it attractive to use small interfering RNAs (siRNAs) as anti-avian flu prophylactics and therapeutics. siRNAs are double stranded RNA duplexes that mediate sequence-specific degradation of mRNA when bound with the RNA-induced silencing complex (RISC) through antisense strand(6,7). It has been reported that siRNAs targeting PA and NP genes of H5N1 virus can effectively inhibit viral replication in cultured cells and provide a prophylactic effect in a mouse model, but cannot offer any significant therapeutic effect(8,9). Therefore, design and identification of more effective siRNAs are urgently needed for the development of RNA interference-based anti-H5N1 agents.